Agmatine : Food for thought....

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    Agmatine : Food for thought....


    Alright everyone. Just wanted to post up some information as i know a lot of you have been using agmatine for nutrient partioning, and pumps ect. This thread is not meant to deter anyone, nor say its a good or bad product. Im a Science guy, i read all the time and when i come across interesting articles, i tend to share them and love hearing feedback and discussion. This is how we all learn.

    I specifically messaged coop about this because he is highly respectable, and has great knowledge. Im hoping this can lead to civil discussion where people can take what they want from it.

    Agmatine study in rats

    Essentially this study had a few groups with agmatine and rats were givin IP shots of the Agmatine. They recorded food intake and Alpha2 activity.

    The study showed that in HIGHER doses, NPY/AgRP levels (hunger signals, carb cravings) were higher. They showed increased appetite and an orexigenic effect. The Amount of food was then tested when agmatine was given with yohimne and still showed an increase yet, Yohimbine attenuated npy plus agmatine stimulated feeding by 30%


    "based on these findings, Agmatine reduces noradrenaline activity in the PVN via pre synaptic a2- adrenoreceptors, which in turn may promote the release of NPY and consequently stimulate eating"

    Theres a lot more in the study, but these were in RATS, and they were injkections. But ive seen people taking up to 2g per day.

    i think this is a good reading especially with summer coming up.... Pump is nice, but when it can come at the expense of an increased food intake and agonism of alpha 2s id be worried.

    This can go hand in hand with what dan duchain said in Bodyopus.... Low calorie dieting can increase alpha 2 receptors. Increases in NPY and AgRP can influence Alpha-2 adrenos, and slow metabolism... This can be shown by rT3 levels.

    increased NPY/AgRP with depressed leptin, increases alpha 2 agonism, and increased food intake can be a cause for disaster in some people

    When N{PY/AgRP are raised there becomes issues with thyroid...

    Theres definitely other mechanisms in here. but i just put down some kind of messy to post this thread,.
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    So basically those high doses of agmatine , can potentially slow down metabolism and A2 receptors? Or is my brain-hamster still asleep and I am not understanding...
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    Now this isnt to say that it is not a good product.

    Agmatine can be touted as an anabolic. Its shown to increas Akt, which can enhance things like.... glut4 translocation, increased protein synthesis, adipogenesis, and glycogen storage.

    It may be an ideal intra workout, with Yohimbine to counteract issues of feeding and attenuate possible issues with agonism at the a2 receptors. Due to its short halflife there may be no issues.

    But again study mentioned above was IN RATS not in humans, so i can not make any conclusions to its efficancy or carry over to humans from the rat study
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    Quote Originally Posted by Celorza View Post
    So basically those high doses of agmatine , can potentially slow down metabolism and A2 receptors? Or is my brain-hamster still asleep and I am not understanding...
    potentially, but as i mentioned it may or may not carry over to humans. Theres potential there, yet not well understood.

    Can it slow down metabolism.... By the looks of the study IN RATs its plausible. I havent seen any human reseach on this. And this study was done with central injections. Not oral administration!
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    Hm...interesting...I wanna hear what Cy has to say about this , he always dumbs this down for my nugget brain and has good input on this things. (I am good with computers...not too much with human chemistry/biology...engineer after all lol)
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    we spoke breifly, not sure he has seen the full study as of yet. Just think it can be a fun discussion. Carrying over to humans is not plausible at all times. So it would be cool to see how everyone takes this study. See how people who use it throughout the day like it while cutting, what they notice.

    This i meant to be an INFORMATIVE thread and nothing else.... where every on can learn from everyone else.

    At this point i have no product with it in there, not plans on it until my research is complete. So i have no vested interest in the posting of this
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    Quote Originally Posted by EBF Inc View Post
    we spoke breifly, not sure he has seen the full study as of yet. Just think it can be a fun discussion. Carrying over to humans is not plausible at all times. So it would be cool to see how everyone takes this study. See how people who use it throughout the day like it while cutting, what they notice.

    This i meant to be an INFORMATIVE thread and nothing else.... where every on can learn from everyone else.

    At this point i have no product with it in there, not plans on it until my research is complete. So i have no vested interest in the posting of this
    You see , this is what makes people like you welcomed in this forums...I rather enjoy reading or participating in an intellectual discussion without background agendas , and just for the sake of letting us all grow smarter and more well informed about what we take and how we take it .

    On a note on this...Slightly slowing metabolism and anabolic abilities might be a good thing for Ectomorphs should this actually carry on to humans , having a real fast metabolism isn't good either, at least not if you want to gain size and don't want to have to spend 200 dollars of food every week just to cover your extensive caloric needs to actually hit surplus right?.
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    Quote Originally Posted by Celorza View Post
    You see , this is what makes people like you welcomed in this forums...I rather enjoy reading or participating in an intellectual discussion without background agendas , and just for the sake of letting us all grow smarter and more well informed about what we take and how we take it .

    On a note on this...Slightly slowing metabolism and anabolic abilities might be a good thing for Ectomorphs should this actually carry on to humans , having a real fast metabolism isn't good either, at least not if you want to gain size and don't want to have to spend 200 dollars of food every week just to cover your extensive caloric needs to actually hit surplus right?.
    It may be perfect like i said intra workout with some gatorade and yohimbine to increase anabolism. the yohimbine can counter POTENTIAL increase in hunger 2-4 hours after agmatine supplementation. Yet you still get all the anabolism but very little if any (due to negated effects???) activity at alpha 2s
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    You forgot the effects it has on the NMDA (antagonist) and on the adreno receptors (On one hand it can be a partial agonist which may increase fat loss or it could be partial antagonist which would halt fat loss)

    Recently this has been the latest craze on the forums. It is sort of the flavor of the month so to speak. It is mainly marketed as something to induce "teh pumps!" but from the looks of it to me, it comes with a couple negatives.

    Agmatine: Biological Role and Therapeutic Potentials in Morphine Analgesia and Dependence

    Agmatine is an amine that is formed by decarboxylation of L-arginine by the enzyme arginine decarboxylase (ADC) and hydrolyzed by the enzyme agmatinase to putrescine. Agmatine binds to several target receptors in the brain and has been proposed as a novel neuromodulator. In animal studies, agmatine potentiated morphine analgesia and reduced dependence/withdrawal. While the exact mechanism is not clear, the interactions with N-methyl-D-aspartate (NMDA) receptors, &amp;alpha;2-adrenergic receptors, and intracellular cyclic adenosine monophosphate (cAMP) signaling have been proposed as possible targets. Like other monoamine transmitter molecules, agmatine is rapidly metabolized in the periphery and has poor penetration into the brain, which limits the use of agmatine itself as a therapeutic agent. However, the development of agmatinase inhibitors will offer a useful method to increase endogenous agmatine in the brain as a possible therapeutic approach to potentiate morphine analgesia and reduce dependence/withdrawal. This review provides a succinct discussion of the biological role/therapeutic potential of agmatine during morphine exposure/pain modulation, with an extensive amount of literature cited for further details.
    FT - http://www.aapsj.org/view.asp?art=aapsj080356

    Agmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor inhibits alpha 2-adrenoceptors.

    It has been suggested that agmatine (decarboxylated arginine) is an endogenous clonidine-displacing substance (CDS) which recognizes 2-adrenoceptor and non-adrenoceptor, imidazoline binding sites. We have examined the effect of agmatine at 2-adrenoceptor binding sites and pre- and postjunctional 2-adrenoceptors. Agmatine produced a concentration-dependent inhibition of 1 nmol/l 3H-clonidine binding to both rat (pKi–5.10+-0.05) and bovine (pKi–4.77+-0.38) cerebral cortex membranes. However, agmatine (0.1–100 M) failed to activate pre-junctional 2-adrenoceptors regulating transmitter release in the guinea-pig isolated ileum and rat isolated vas deferens, nor did it activate post-junctional 2-adrenoceptors of the porcine isolated palmar lateral vein which mediate contraction or inhibition of forskolin-stimulated cyclic AMP formation. High concentrations of agmatine (10–30-fold the pKi at 2-adrenoceptor binding sites) failed to influence 2-adrenoceptor activation by either clonidine or UK-14304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate) in any of the peripheral preparations examined. Moreover, even in a preparation where an interaction with 2-adrenoceptor binding sites on cell membranes can be demonstrated, the rat cerebral cortex, agmatine failed to inhibit forskolin-stimulated cyclic AMP in the intact tissue or affect the inhibition produced by the selective 2-adrenoceptor agonist UK-14304. Agmatine was also devoid of agonist activity in two preparations, the rat isolated thoracic aorta and the rat isolated gastric fundus, in which CDS has been reported to produce non-adrenoceptor effects. Thus, we have confirmed that agmatine recognizes 2-adrenoceptor binding sites and, therefore, is a CDS. However, since agmatine is devoid of pharmacological activity at either peripheral or central 2-adrenoceptors it can not account for earlier reports suggesting that brain-derived CDS can activate 2-adrenoceptors.
    Cardiovascular responses to agmatine, a clonidine-displacing substance, in anesthetized rat.

    We investigated the cardiovascular responses in anesthetized ventilated rats to agmatine (decarboxylated arginine), an amine which is an endogenous clonidine-displacing substance (CDS) synthesized in brain. Intracisternal agmatine dose-dependently increased sympathetic nerve activity and arterial pressure (at 400 nmol by 8.7 +/- 2.1 microV and 28.6 +/- 2.7 mmHg, respectively) and blocked arterial baroreflex reflexes. Microinjection of agmatine into the rostral ventrolateral medulla (RVL) had no effect on arterial pressure or sympathetic nerve activity while iontophoresis of agmatine onto defined vasomotor neurons of RVL was also without effect. Agmatine (i.v.) decreased sympathetic nerve activity and arterial pressure probably by blocking the transmission through sympathetic ganglia and by direct dilation of vascular smooth muscles. Despite binding like clonidine to alpha 2-adrenergic receptors and imidazoline (I)-receptors of both classes, agmatine does not replicate the central or peripheral actions of clonidine. The results suggest that earlier cardiovascular actions of partially purified CDS were either attributable to contaminating molecules and/or that CDS may be a family of molecules.
    Cardiovascular effects of agmatine, a "clonidine-displacing substance", in conscious rabbits.

    Agmatine has been identified as a "clonidine-displacing substance" in extracts from bovine brain. We studied its effect on cardiovascular regulation and the role played in this effect by alpha 2-adrenoceptors. In conscious rabbits, agmatine 10 micrograms kg-1 injected intracisternally (i.c.) caused no change, whereas agmatine 30, 100 and 300 micrograms kg-1 i.c. increased renal sympathetic nerve firing, the plasma concentration of noradrenaline and adrenaline and arterial blood pressure. Heart rate tended to be decreased. Yohimbine 1.5 micrograms kg-1 i.c. caused no change, whereas yohimbine 5, 15 and 50 micrograms kg-1 increased renal sympathetic nerve activity, the plasma concentration of noradrenaline and adrenaline, blood pressure and heart rate. In rabbit brain cortex slices preincubated with [3H]-noradrenaline, agmatine 1 to 100 microM did not modify the electrically evoked overflow of tritium (either 4 pulses at 100 Hz or 36 pulses at 3 Hz). The evoked overflow was reduced by 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304) 0.03 to 30 nM (4 pulses at 100 Hz), and this inhibition was not affected by agmatine 10 and 100 microM. Agmatine did not change the basal efflux of tritium. The results show that agmatine, like yohimbine, causes central sympathoexcitation when given i.c., but agmatine differs from yohimbine in that it does not increase heart rate. Agmatine acts neither as an agonist nor as an antagonist at the alpha 2-autoreceptors in rabbit brain cortex. alpha 2-Adrenoceptors, therefore, are probably not involved in its cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)
    Agmatine: an endogenous clonidine-displacing substance in the brain.

    Clonidine, an antihypertensive drug, binds to alpha 2-adrenergic and imidazoline receptors. The endogenous ligand for imidazoline receptors may be a clonidine-displacing substance, a small molecule isolated from bovine brain. This clonidine-displacing substance was purified and determined by mass spectroscopy to be agmatine (decarboxylated arginine), heretofore not detected in brain. Agmatine binds to alpha 2-adrenergic and imidazoline receptors and stimulates release of catecholamines from adrenal chromaffin cells. Its biosynthetic enzyme, arginine decarboxylase, is present in brain. Agmatine, locally synthesized, is an endogenous agonist at imidazoline receptors, a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter.
    So it is an antagonist for NDMA receptor and agonist for the alpha 2

    Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery.

    1. We investigated the vascular effects of agmatine (decarboxylated arginine), an endogenous ligand for alpha 2-adrenoceptors and non-adrenoceptor imidazoline (I-) receptors, present in endothelium, smooth muscle and plasma, using the rat tail artery as a model. 2. While by itself agmatine (10 nM-1 mM) was without effect on isolated arterial rings, at the highest concentration used (1 mM) it slightly increased EC50 values for contractions elicited respectively by the alpha 1- and alpha 2- adrenoceptor agonists methoxamine and clonidine. 3. Agmatine (0.03-1 mM) produced a concentration-dependent transient inhibition of the contractions induced by transmural nerve stimulation (TNS; 200 mA, 0.2 ms, 1 Hz, 10 s). This effect was abolished by the alpha 2-adrenoceptor antagonists, rawolscine and idazoxan. 4. In the presence of rawolscine or idazoxan, agmatine produced a concentration-dependent delayed facilitation of TNS-induced contractions, which was prevented by cocaine. 5. Neither inhibitory nor potentiating actions were produced by agmatine on contractions induced by noradrenaline (NA) administration. 6. Agmatine did not directly affect [3H]-NA uptake in bovine cultured chromaffin cells. 7. Agmatine can regulate vascular function by two opposing actions at sympathetic nerve terminals, with different latencies: a transient inhibition of NA release mediated by prejunctional alpha 2-adrenoceptors and a cocaine-sensitive delayed facilitation the mechanism of which is undetermined at present. 8. The results reveal the existence of a novel endogenous amine modulating NA release in the perivascular sympathetic terminals.
    And also looks like agmatine can inhibit NA release (agonizes Aplha 2)

    Combine these with its potential to increase hunger hormones NPY/AgRP and you have the reasons why I dont mess with it.

    Also to be fair, this hasnt been shown in humans so it isnt really too straightforward but to me the potential is there which makes me be cautious with its use.
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    I still haven't gotten around to reading past the abstract (50% my fault for being lazy) but I will set aside some time tonight for sure
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    Quote Originally Posted by mr.cooper69
    I still haven't gotten around to reading past the abstract (50% my fault for being lazy) but I will set aside some time tonight for sure
    All good brotha. Look forward to the discussion. Glad I had the full study of something you haven't read yet.
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    Agmatine Stimulates Hepatic Fatty Acid Oxidation


    i can`t post attachments (don`t know why??)

    but take a look on post #18 Sir

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    Very interesting articles and discussion.
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    Sub'd

    Good thread
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    Quote Originally Posted by Clickster
    Very interesting articles and discussion.
    x2.
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    Quote Originally Posted by MAxximal
    i can`t post attachments (don`t know why??)

    but take a look on post #18 Sir

    Augmatine
    Excellent study. The one I posted spoke about decrease norepinephrine

    Maybe I'll try it on my bulk. I have yet to decide. Overall benefits are there. But still worrysome
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    A couple thoughts as I read through the study posted on the OP:

    -Agmatine is widely distributed throughout the brain and acts as a regulatory molecule in many instances. Direct injection into the PVN may be creating a reductionist view of its systemic effects.
    -Given agmatine's brief serum half-life and associated correlation to the A2-adrenoreceptor, it comes as no surprise that appetite was increased only briefly following agmatine administration and normalized after two hours at the latest (see i.p. injections). The PVN injections showed a similar, albeit slower phenomenon. The effects on appetite are also dose-dependent, and we presently have no means for calculating the oral bioavailability/dose from injections.
    -When they added clonidine to the mix, the data conflicted with the previous assessment. aCSF + agmatine actually tended to a decrease in appetite over the control in 5 nmol agmatine-treated rats. However, the data with the yohimbine played out as expected. Again, it is important to note that yohimbine can suppress appetite by means besides a2 antagonism (5ht), so the study is not without confounding factors.
    -The authors note that the increase in 24 hour food intake are simply a carryover from the initial 2 hours. This is again related to the half-life of agmatine and shows that the increase in appetite is rather short-lived.
    -I have good reason to believe that the demonstrated effect on 24-hour food consumption would be nearly negligible in humans. I don't see any agmatine users reporting a 350% increase in appetite for 2 hours following their agmatine dose. Many of us are highly diet-conscious and would notice it if we suddenly became ravenous. My suspicion is that concentrations resulting from the i.p./PVN injections at the doses they used are simply not matched in oral consumption and/or distribution. Remember, the effect was non-existent at lower concentrations.

    All of the above said, this study has plenty of important implications. It elucidates yet another mechanism by which agmatine acts (this compound is truly involved in a ton of processes). If the doses used in the study are relevant to the oral doses we are taking (for which I'm leaning towards the stance that they are not), agmatine would be favorable on a bulk and should be administered with a stimulant (caffeine, yohimbine, ephedrine, 1,3D, even synehprine) on a cut so that appetite is suppressed within the 2 hours following consumption.

    Great read EBF, thanks!
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    Quote Originally Posted by mr.cooper69 View Post
    A couple thoughts as I read through the study posted on the OP:

    -Agmatine is widely distributed throughout the brain and acts as a regulatory molecule in many instances. Direct injection into the PVN may be creating a reductionist view of its systemic effects.
    -Given agmatine's brief serum half-life and associated correlation to the A2-adrenoreceptor, it comes as no surprise that appetite was increased only briefly following agmatine administration and normalized after two hours at the latest (see i.p. injections). The PVN injections showed a similar, albeit slower phenomenon. The effects on appetite are also dose-dependent, and we presently have no means for calculating the oral bioavailability/dose from injections.
    -When they added clonidine to the mix, the data conflicted with the previous assessment. aCSF + agmatine actually tended to a decrease in appetite over the control in 5 nmol agmatine-treated rats. However, the data with the yohimbine played out as expected. Again, it is important to note that yohimbine can suppress appetite by means besides a2 antagonism (5ht), so the study is not without confounding factors.
    -The authors note that the increase in 24 hour food intake are simply a carryover from the initial 2 hours. This is again related to the half-life of agmatine and shows that the increase in appetite is rather short-lived.
    -I have good reason to believe that the demonstrated effect on 24-hour food consumption would be nearly negligible in humans. I don't see any agmatine users reporting a 350% increase in appetite for 2 hours following their agmatine dose. Many of us are highly diet-conscious and would notice it if we suddenly became ravenous. My suspicion is that concentrations resulting from the i.p./PVN injections at the doses they used are simply not matched in oral consumption and/or distribution. Remember, the effect was non-existent at lower concentrations.

    All of the above said, this study has plenty of important implications. It elucidates yet another mechanism by which agmatine acts (this compound is truly involved in a ton of processes). If the doses used in the study are relevant to the oral doses we are taking (for which I'm leaning towards the stance that they are not), agmatine would be favorable on a bulk and should be administered with a stimulant (caffeine, yohimbine, ephedrine, 1,3D, even synehprine) on a cut so that appetite is suppressed within the 2 hours following consumption.

    Great read EBF, thanks!
    Now this is why I subscribed , Cy always lets me understand it easily haha. A truly fascinating thing Agmatine...comes with a lot of added benefits it seems , and! I did say it would be beneficial on a bulk so I did get the main point ^^!!
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    Too lazy to read through study tonight (gimme a break its late) but will definitely be back through to read it tomorrow!
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    Quote Originally Posted by mr.cooper69
    A couple thoughts as I read through the study posted on the OP:

    -Agmatine is widely distributed throughout the brain and acts as a regulatory molecule in many instances. Direct injection into the PVN may be creating a reductionist view of its systemic effects.
    -Given agmatine's brief serum half-life and associated correlation to the A2-adrenoreceptor, it comes as no surprise that appetite was increased only briefly following agmatine administration and normalized after two hours at the latest (see i.p. injections). The PVN injections showed a similar, albeit slower phenomenon. The effects on appetite are also dose-dependent, and we presently have no means for calculating the oral bioavailability/dose from injections.
    -When they added clonidine to the mix, the data conflicted with the previous assessment. aCSF + agmatine actually tended to a decrease in appetite over the control in 5 nmol agmatine-treated rats. However, the data with the yohimbine played out as expected. Again, it is important to note that yohimbine can suppress appetite by means besides a2 antagonism (5ht), so the study is not without confounding factors.
    -The authors note that the increase in 24 hour food intake are simply a carryover from the initial 2 hours. This is again related to the half-life of agmatine and shows that the increase in appetite is rather short-lived.
    -I have good reason to believe that the demonstrated effect on 24-hour food consumption would be nearly negligible in humans. I don't see any agmatine users reporting a 350% increase in appetite for 2 hours following their agmatine dose. Many of us are highly diet-conscious and would notice it if we suddenly became ravenous. My suspicion is that concentrations resulting from the i.p./PVN injections at the doses they used are simply not matched in oral consumption and/or distribution. Remember, the effect was non-existent at lower concentrations.

    All of the above said, this study has plenty of important implications. It elucidates yet another mechanism by which agmatine acts (this compound is truly involved in a ton of processes). If the doses used in the study are relevant to the oral doses we are taking (for which I'm leaning towards the stance that they are not), agmatine would be favorable on a bulk and should be administered with a stimulant (caffeine, yohimbine, ephedrine, 1,3D, even synehprine) on a cut so that appetite is suppressed within the 2 hours following consumption.

    Great read EBF, thanks!
    Great post.

    Like I said. This was centrally administered. So effects are different. I've still yet to try what I mentioned.

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    I've tried Primaforce Agmatine, AI Agmatine back last year, recent got a bottle of Synthetic Sups Agmatine and been waiting to get samples of SNS Agmatine (I need to resubmit).

    I'm curious to know if people have had better results with 1 brand over another.

    (Don't want this to start an argument, just curious to see who can feel which one working cause apparently there maybe some differences)
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    Quote Originally Posted by AaronJP1
    I've tried Primaforce Agmatine, AI Agmatine back last year, recent got a bottle of Synthetic Sups Agmatine and been waiting to get samples of SNS Agmatine (I need to resubmit).

    I'm curious to know if people have had better results with 1 brand over another.

    (Don't want this to start an argument, just curious to see who can feel which one working cause apparently there maybe some differences)
    I've noticed better results from SNS than I did with Smart Powders, for whatever reason. SP did almost nothing at 1g/day, through the whole month. Those are the only two I've had stand alone. Most of my use is in Hemavol.
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    Quote Originally Posted by TheGilmore

    I've noticed better results from SNS than I did with Smart Powders, for whatever reason. SP did almost nothing at 1g/day, through the whole month. Those are the only two I've had stand alone. Most of my use is in Hemavol.
    How many times a week do u use Hemavol?
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    Ive had great results using SNS brand as well. Now trying Synthetic Supplements version.
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    Quote Originally Posted by AaronJP1

    How many times a week do u use Hemavol?
    When I have it, I use 2 scoops preworkout. So, 4-5 times a week.
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    Quote Originally Posted by TheGilmore

    When I have it, I use 2 scoops preworkout. So, 4-5 times a week.
    Nice.
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    Good reads.
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    might be a stupid question but if its an nmda antagonist shouldn't it mess u up like ketamine, phencyclidine (PCP) or high dose dextromethorphan.

    A lot of the sciencey stuff in this thread kind of goes over my head but it would explain why my weight loss has slowed and my appetite has increased. gotta love the pumps though almost as nice as bustin a nut.
    Last edited by Oscar; 05-27-2012 at 01:06 PM. Reason: didn't realize you cant cuss here
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    I'm currently using 1g daily all dosed first thing in the morning on an empty stomach 30-45 min prior to my first meal. I'm using it primarily for analgesic purposes, but I am using it while currently doing a slow cut and/or recomp. I will also keep an eye out for any slowing of weight loss and or increased appettite. I plan to run agmatine for the next few months.
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    subbed
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    The more posts we have with regards to weightless/weight gain the more information we can put together and see what correlates to the studies and what doesn't.

    Can't wait for more posts
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    So i should or shouldnt dose agmatine on my Intimidate run?
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    Interesting thread and discussion going, I like this
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    Quote Originally Posted by theniteman View Post
    So i should or shouldnt dose agmatine on my Intimidate run?
    Definitely do.

    Agmatine is said to serve as an endogenous neuroprotective neuromodulator which is co-released during neurotransmitter release. Agmatine is a specific competitive antagonist of the NMDA receptor and it's guanidine moiety makes it different than traditional NMDA receptor antagonists. The important thing to distinguish here is that exogenous application of Agmatine and D-Aspartic acid work on different mechanisms for the NMDA receptor, so regardless of one being an antagonist and the other an agonist, they do not overlap. Exogenous D-aspartic acid application utilizes the R-type VGCCs and none of the others, while exogenous Agmatine is said to use the L-type VGCCs and shows no signs of inhibition of the R-type VGCCs.

    Another important thing to note is that Agmatine was found as an effective preventative method when it comes to glutamatergic NMDA cell death.
    From Synapsin:

    I wrote about something similar to this else where, so let me go into some detail about the NMDA receptor (easy to find anywhere, nothing original here besides some concepts I was personally toying with, and I should note it was done on my phone so don't get mad if my grammar is poor):


    "The NMDA receptor is an ionotropic receptor that allows for the transfer of electrical signals between neurons in the brain and in the spinal column. For electrical signals to pass, the NMDA receptor must be open. To remain open, an NMDA receptor must bind to glutamate and to glycine. An NMDA receptor that is bound to glycine and glutamate and has an open ion channel is called "activated."

    NMDA receptors aren't activated easily. The receptor is blocked by Mg2+ so it needs to have sufficient depolarization. Even if you have Aspartic acid there (or Glutamate), you need Glycine to be there as well. So you need a few things at once to activate the NMDA receptors, the key thing being the depolarization of say an AMPA receptor near by before any of the binding even matters. Test force gets around the issue of Glycine by using Sarcosine.

    NMDA receptors have different subunits, and the effects of the subunits upon activation. Basic message to take home is that DAA is likely not going to elicit toxicity (due to A and B noted below) because toxicity most likely only comes from NR2B subunit. But if it DOES elicist neurotoxicity, keep reading on how to address this.


    A) NR2B-NR2A developmental switch (hypothesis)
    B) NR2A probably has a higher affinity than NR2B when it comes L/D-Aspartate


    Chemicals that deactivate the NMDA receptor are called antagonists. NMDAR antagonists fall into four categories:

    1) Competitive antagonists, which bind to and block the binding site of the neurotransmitter glutamate;
    2) Glycine antagonists, which bind to and block the glycine site;
    3) Noncompetitive antagonists, which inhibit NMDARs by binding to allosteric sites; and
    4) Uncompetitive antagonists, which block the ion channel by binding to a site within it."

    Something worthy of a read:

    "Agmatine Selectively Blocks theN-Methyl-d-Aspartate Subclass of Glutamate Receptor Channels in Rat Hippocampal Neurons1

    Abstract

    We investigated in rat hippocampus neurons whether 4-(aminobutyl)guanidine (agmatine), formed by decarboxylation ofl-arginine by arginine decarboxylase and metabolized to urea and putrescine, can modulate the function ofN-methyl-d-aspartate (NMDA) receptor channels. In cultured hippocampal neurons studied by whole-cell patch clamp, extracellular-applied agmatine produced a voltage- and concentration-dependent block of NMDA but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid nor kainate currents. Analysis of the voltage dependence of the block suggests that agmatine binds at a site located within the NMDA channel pore with a dissociation constant of 952 μM at 0 mV and an electric distance of 0.62. We also tested effects of several agmatine analogs. Arcaine (1,4-butyldiguanidine) also produced a similar voltage-dependent block of the NMDA current, whereas putrescine (1,4-butyldiamine) had little effect, suggesting that the guanidine group of agmatine is the active moiety when blocking the NMDA channel. Moreover, spermine (an endogenous polyamine) potentiated the NMDA current even in the presence of blocker agmatine or arcaine, suggesting that the guanidine-containing compounds agmatine and arcaine interact with the NMDA channel at a binding site different from that of spermine. Our results indicate that in hippocampal neurons agmatine selectively modulates the NMDA subclass of glutamate receptor channels mediated by the interaction between the guanidine group and the channel pore. The results support other data that agmatine may function as an endogenous neurotransmitter/neuromodulator in brain."

    Also:

    Effect of Agmatine Against Cell Death Induced by NMDA and Glutamate in Neurons and PC12 Cells

    "Therefore, it is conceivable that agmatine, coreleased with glutamate, may act to
    inhibit the activation of NMDA receptors during conditions leading to higher glutamate
    release. Further in vivo studies, measuring the release of agmatine along with
    glutamate are required to verify this hypothesis.
    In summary, we have provided evidence that agmatine is a neuroprotective
    molecule and reduces excitotoxic cell death induced by glutamate or NMDA.

    .....

    Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons."

    "Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property."

    Another thing to keep in mind from the paper I just pasted above:

    "Because axons that innervate pyramidal cells are glutamatergic and
    pyramidal cells expressNMDAsubclass of glutamate receptors, it has been proposed
    that agmatine may be costored and released with glutamate as a counterregulatory
    molecule. Electrophysiological studies of cultured hippocampal neurons have also
    supported the contention that agmatine selectively inhibitedNMDAchannels (Yang
    and Reis, 1999).

    While these previous studies suggested a possible regulatory role for agmatine
    in normal glutamatergic neurotransmission, agmatine may also play a role in pathological conditions involving higher activation ofNMDAreceptors. Thus, agmatine
    is protective against ischemic injury (Gilad, 1996b), spinal cord injury (Fairbanks
    et al., 2000; Gilad and Gilad 2000; Yu et al., 2000) and neuropathic pain (Fairbanks
    et al., 1998), conditions that arise from higher NMDA receptor activation and are
    reversed byNMDAreceptor antagonists. The present study has provided further evidence
    that the neuroprotective action of agmatine could be mediated by the blockade
    of NMDA receptors."

    Dr. Houser was actually asked this before (http://www.*************/forum/ask-dr...-question.html)

    Anyhow, I wrote a post about this on a different forum concerning DAA and something with a similar concept to Agmatine in terms of neuroprotective methods, Huperzine A.

    Some key differences though:

    "Agmatine Fails to Inhibit Cell Death Induced by Calcimycin or Staurosporin
    To address the question whether the effect of agmatine on cell death is mediated
    by nonspecific blockade of cation channels or by inhibiting intracellular protein
    kinase pathways, we investigated other nonexcitoxic cell death models. Calcimycin,
    a calcium channel opener, caused a significant increase in LDH release in neurons
    (4% vs. 11.5%) and PC12 (4% vs. 12%) cells, indicating marked cell death (Fig. 5).
    Agmatine (100 ¹M), when incubated with calcimycin, failed to inhibit the elevated
    release of LDH.Asimilar result was obtained with staurosporin, which causes apoptotic
    cell death by intracellular actions, where LDH release was not inhibited by
    agmatine (100 ¹M) in neurons and PC12 cells (Fig. 5)."

    What I said about Huperzine A:

    "Huperzine A (?100 µM) had no effect on the binding of [3H]glutamate (low- and high-affinity glutamate sites), [3H]MDL 105,519 (NMDA glycine regulatory site), [3H]ifenprodil (NMDA polyamine site) or [3H]CGS 19755 (NMDA antagonist). These are the things we really worry about when we talk about DAA and NMDA receptors.

    In contrast with these results, HUP-A non-competitively (Hill slope < 1) inhibited [3H]MK-801 and [3H]TCP binding (co-located NMDA ion channel PCP site) with pseudo Ki ? 6 µM.

    Therefore, HUP-A most likely attenuates excitatory amino acid toxicity by blocking the NMDA ion channel and subsequent Ca2+ mobilization at or near the PCP and MK-801 ligand sites."

    Now that we have all that said, key thing to keep in mind, once the NMDA receptor is activated (takes a few things to be activated), that is it, it will release the neurotransmitter. If glutamate induced NMDA activation is co-activated with Agmatine release, I would assume that taking DAA will also increase endogenous Agmatine release in order to protect you from glutamatergic neurotoxicity. We can sort of thing of Agmatine as acting as a buffer to keep DAA from over exciting NDMA receptors.

    We have DAA present (check, so more NMDA activation now with Glycine, Ca+2 current, agonist DAA here), Agmatine doesn't affect Calcium intracellular mechanisms (check, you need the depolarization to stop the Mg+2 from blocking the site), Glycine present (will happen for activation of the receptor, so check). Say the NMDA receptor is now activated, releases Glutamate, blah blah blah, the Agmatine in the product in theory based on what I posted above is also endogenously released, so exogenous application will enhance that regulatory role of Agmatine so that in higher levels of NMDA receptor activation, it will inhibit the receptor from higher glutamate release (so overexcitation leading to potential neurotoxicity) by inhibting the receptor. Basically Agmatine might be able to prevent the neurotoxicity you always hear about when talking about DAA by preventing overexcitation of NMDA receptors/ reversing the levels of activation.
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    My skinny asss is always bulking .. I've dosed. 750mg-1g on workout days for. 6weeks

    Dont know if I can report much on increase hunger .. But on my next run I'll keep an eye on it
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    Awesome thx Coop for the info.!
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    Quote Originally Posted by mr.cooper69

    Definitely do.

    From Synapsin:

    I wrote about something similar to this else where, so let me go into some detail about the NMDA receptor (easy to find anywhere, nothing original here besides some concepts I was personally toying with, and I should note it was done on my phone so don't get mad if my grammar is poor):

    "The NMDA receptor is an ionotropic receptor that allows for the transfer of electrical signals between neurons in the brain and in the spinal column. For electrical signals to pass, the NMDA receptor must be open. To remain open, an NMDA receptor must bind to glutamate and to glycine. An NMDA receptor that is bound to glycine and glutamate and has an open ion channel is called "activated."

    NMDA receptors aren't activated easily. The receptor is blocked by Mg2+ so it needs to have sufficient depolarization. Even if you have Aspartic acid there (or Glutamate), you need Glycine to be there as well. So you need a few things at once to activate the NMDA receptors, the key thing being the depolarization of say an AMPA receptor near by before any of the binding even matters. Test force gets around the issue of Glycine by using Sarcosine.

    NMDA receptors have different subunits, and the effects of the subunits upon activation. Basic message to take home is that DAA is likely not going to elicit toxicity (due to A and B noted below) because toxicity most likely only comes from NR2B subunit. But if it DOES elicist neurotoxicity, keep reading on how to address this.

    A) NR2B-NR2A developmental switch (hypothesis)
    B) NR2A probably has a higher affinity than NR2B when it comes L/D-Aspartate

    Chemicals that deactivate the NMDA receptor are called antagonists. NMDAR antagonists fall into four categories:

    1) Competitive antagonists, which bind to and block the binding site of the neurotransmitter glutamate;
    2) Glycine antagonists, which bind to and block the glycine site;
    3) Noncompetitive antagonists, which inhibit NMDARs by binding to allosteric sites; and
    4) Uncompetitive antagonists, which block the ion channel by binding to a site within it."

    Something worthy of a read:

    "Agmatine Selectively Blocks theN-Methyl-d-Aspartate Subclass of Glutamate Receptor Channels in Rat Hippocampal Neurons1

    Abstract

    We investigated in rat hippocampus neurons whether 4-(aminobutyl)guanidine (agmatine), formed by decarboxylation ofl-arginine by arginine decarboxylase and metabolized to urea and putrescine, can modulate the function ofN-methyl-d-aspartate (NMDA) receptor channels. In cultured hippocampal neurons studied by whole-cell patch clamp, extracellular-applied agmatine produced a voltage- and concentration-dependent block of NMDA but not ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid nor kainate currents. Analysis of the voltage dependence of the block suggests that agmatine binds at a site located within the NMDA channel pore with a dissociation constant of 952 ?M at 0 mV and an electric distance of 0.62. We also tested effects of several agmatine analogs. Arcaine (1,4-butyldiguanidine) also produced a similar voltage-dependent block of the NMDA current, whereas putrescine (1,4-butyldiamine) had little effect, suggesting that the guanidine group of agmatine is the active moiety when blocking the NMDA channel. Moreover, spermine (an endogenous polyamine) potentiated the NMDA current even in the presence of blocker agmatine or arcaine, suggesting that the guanidine-containing compounds agmatine and arcaine interact with the NMDA channel at a binding site different from that of spermine. Our results indicate that in hippocampal neurons agmatine selectively modulates the NMDA subclass of glutamate receptor channels mediated by the interaction between the guanidine group and the channel pore. The results support other data that agmatine may function as an endogenous neurotransmitter/neuromodulator in brain."

    Also:

    Effect of Agmatine Against Cell Death Induced by NMDA and Glutamate in Neurons and PC12 Cells

    "Therefore, it is conceivable that agmatine, coreleased with glutamate, may act to
    inhibit the activation of NMDA receptors during conditions leading to higher glutamate
    release. Further in vivo studies, measuring the release of agmatine along with
    glutamate are required to verify this hypothesis.
    In summary, we have provided evidence that agmatine is a neuroprotective
    molecule and reduces excitotoxic cell death induced by glutamate or NMDA.

    .....

    Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons."

    "Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property."

    Another thing to keep in mind from the paper I just pasted above:

    "Because axons that innervate pyramidal cells are glutamatergic and
    pyramidal cells expressNMDAsubclass of glutamate receptors, it has been proposed
    that agmatine may be costored and released with glutamate as a counterregulatory
    molecule. Electrophysiological studies of cultured hippocampal neurons have also
    supported the contention that agmatine selectively inhibitedNMDAchannels (Yang
    and Reis, 1999).

    While these previous studies suggested a possible regulatory role for agmatine
    in normal glutamatergic neurotransmission, agmatine may also play a role in pathological conditions involving higher activation ofNMDAreceptors. Thus, agmatine
    is protective against ischemic injury (Gilad, 1996b), spinal cord injury (Fairbanks
    et al., 2000; Gilad and Gilad 2000; Yu et al., 2000) and neuropathic pain (Fairbanks
    et al., 1998), conditions that arise from higher NMDA receptor activation and are
    reversed byNMDAreceptor antagonists. The present study has provided further evidence
    that the neuroprotective action of agmatine could be mediated by the blockade
    of NMDA receptors."

    Dr. Houser was actually asked this before (http://www.*************/forum/ask-dr...-question.html)

    Anyhow, I wrote a post about this on a different forum concerning DAA and something with a similar concept to Agmatine in terms of neuroprotective methods, Huperzine A.

    Some key differences though:

    "Agmatine Fails to Inhibit Cell Death Induced by Calcimycin or Staurosporin
    To address the question whether the effect of agmatine on cell death is mediated
    by nonspecific blockade of cation channels or by inhibiting intracellular protein
    kinase pathways, we investigated other nonexcitoxic cell death models. Calcimycin,
    a calcium channel opener, caused a significant increase in LDH release in neurons
    (4% vs. 11.5%) and PC12 (4% vs. 12%) cells, indicating marked cell death (Fig. 5).
    Agmatine (100 ¹M), when incubated with calcimycin, failed to inhibit the elevated
    release of LDH.Asimilar result was obtained with staurosporin, which causes apoptotic
    cell death by intracellular actions, where LDH release was not inhibited by
    agmatine (100 ¹M) in neurons and PC12 cells (Fig. 5)."

    What I said about Huperzine A:

    "Huperzine A (?100 µM) had no effect on the binding of [3H]glutamate (low- and high-affinity glutamate sites), [3H]MDL 105,519 (NMDA glycine regulatory site), [3H]ifenprodil (NMDA polyamine site) or [3H]CGS 19755 (NMDA antagonist). These are the things we really worry about when we talk about DAA and NMDA receptors.

    In contrast with these results, HUP-A non-competitively (Hill slope < 1) inhibited [3H]MK-801 and [3H]TCP binding (co-located NMDA ion channel PCP site) with pseudo Ki ? 6 µM.

    Therefore, HUP-A most likely attenuates excitatory amino acid toxicity by blocking the NMDA ion channel and subsequent Ca2+ mobilization at or near the PCP and MK-801 ligand sites."

    Now that we have all that said, key thing to keep in mind, once the NMDA receptor is activated (takes a few things to be activated), that is it, it will release the neurotransmitter. If glutamate induced NMDA activation is co-activated with Agmatine release, I would assume that taking DAA will also increase endogenous Agmatine release in order to protect you from glutamatergic neurotoxicity. We can sort of thing of Agmatine as acting as a buffer to keep DAA from over exciting NDMA receptors.

    We have DAA present (check, so more NMDA activation now with Glycine, Ca+2 current, agonist DAA here), Agmatine doesn't affect Calcium intracellular mechanisms (check, you need the depolarization to stop the Mg+2 from blocking the site), Glycine present (will happen for activation of the receptor, so check). Say the NMDA receptor is now activated, releases Glutamate, blah blah blah, the Agmatine in the product in theory based on what I posted above is also endogenously released, so exogenous application will enhance that regulatory role of Agmatine so that in higher levels of NMDA receptor activation, it will inhibit the receptor from higher glutamate release (so overexcitation leading to potential neurotoxicity) by inhibting the receptor. Basically Agmatine might be able to prevent the neurotoxicity you always hear about when talking about DAA by preventing overexcitation of NMDA receptors/ reversing the levels of activation.
    Excellent coop


    Being a guanadine signigicant glucose control can be obtained.

    I am now thinking of trying it with an herbal powder I am personally familiar with n will pm you once complete
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    Quote Originally Posted by JudoJosh
    You forgot the effects it has on the NMDA (antagonist) and on the adreno receptors (On one hand it can be a partial agonist which may increase fat loss or it could be partial antagonist which would halt fat loss)

    Recently this has been the latest craze on the forums. It is sort of the flavor of the month so to speak. It is mainly marketed as something to induce "teh pumps!" but from the looks of it to me, it comes with a couple negatives.

    FT - http://www.aapsj.org/view.asp?art=aapsj080356

    So it is an antagonist for NDMA receptor and agonist for the alpha 2

    And also looks like agmatine can inhibit NA release (agonizes Aplha 2)

    Combine these with its potential to increase hunger hormones NPY/AgRP and you have the reasons why I dont mess with it.

    Also to be fair, this hasnt been shown in humans so it isnt really too straightforward but to me the potential is there which makes me be cautious with its use.
    Nice find judo definitely interested in the conversation. I imagine just like any supplement there are pros and cons to utilizing it. Along with everything in moderation.
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    so daa would actually be a good thing to take along with agmatine?

    i was interesting in taking daa in the morning for a test boost and then agmatine/cit malate preworkout for pump/sex benefits
  

  
 

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